Formation of amygdalin/ß-cyclodextrin derivatives inclusion complexes for anticancer activity assessment in human cervical carcinoma HeLa cell line.

Nanoencapsulation has gained considerable attention because of its unique features and advantages in anticancer drug delivery. Amygdalin (AMY) is an anticancer compound, showing limitations in its applications by low stability. Herein, the inclusion complexes (ICs) of AMY with ß-cyclodextrin (ßCD), and its derivatives such as 2-hydroxypropyl-ßCD (HPßCD) and methyl-ßCD (MßCD) were fabricated. The fabricated AMY/CD-ICs were thoroughly evaluated using Fourier-transform infrared spectroscopy, powder X-ray diffraction, thermogravimetric/differential thermal analysis, proton nuclear magnetic resonance, ultraviolet-visible diffuse reflectance spectroscopy, and photoluminescence techniques. Double reciprocal profile study of the absorption and fluorescence spectra revealed that the AMY formed the ICs with ßCD derivatives at a guest/host stoichiometric ratio of 1/1. The thermal stability of AMY was enhanced as the IC formation aid observed by the shift of thermal degradation temperature of AMY from the range of âˆ¼ 220-250 °C to > 295 °C. Theoretical analyses of the energetic, electronic, and global reactivity parameters of the AMY/CD-ICs were evaluated using the PM3 method. Further assessment of the dissolution diagrams of AMY/CD-ICs revealed a burst release profile. In addition, cell toxicity was evaluated using the MTT assay, and the results showed that AMY/CD-ICs had significantly more efficacious in inhibiting HeLa cancer cells than AMY. These results proved that the IC formations with CDs significantly enhanced the anticancer activity of AMY.

Tuning the efficacy of decellularized apple by coating with alginate/gelatin to behave as a bioscaffold for cultured meat production.

Substantial efforts are underway to tackle the current challenges of sustainability and environmental impacts linked to orthodox animal agriculture. This had led to advancement in food innovation guiding the fabrication of edible scaffolds based cultured meat. This current research work aims to develop and validate a new approach in fabricating a 3D porous scaffold of decellularized apple coated with a polymer mixture of gelatin/alginate for cultivated meat production. The fabricated noncoated (A) and coated (CA) 3D scaffolds presented different ratios of pore sizes with the medium-sized pores (100-250 µm) being higher in the case of CA. The water absorption capacity of CA (∼64 %) was almost two folds compared to A (∼31 %) with delayed digestion in the presence of gastric simulated juice with or without pepsin. Both the scaffolds showed the capability to adhere and proliferate muscle satellite cells as single cell culture and muscle satellite along with NIH/3T3 fibroblast cells as co-culture. However, the CA scaffolds showed enhanced capability to adhere and proliferate the two cell lines on its surface compared to A. This work demonstrates an efficient way to fabricate decellularized plant scaffolds with high potential to be used in the production of cultured meat for the food industry.

Synthetic and biopolymers-based antimicrobial hybrid hydrogels: a focused review.

The constantly accelerating occurrence of microbial infections and their antibiotic resistance has spurred advancement in the field of material sciences and has guided the development of novel materials with anti-bacterial properties. To address the clinical exigencies, the material of choice should be biodegradable, biocompatible, and able to offer prolonged antibacterial effects. As an attractive option, hydrogels have been explored globally as a potent biomaterial platform that can furnish essential antibacterial attributes owing to its three-dimensional (3D) hydrophilic polymeric network, adequate biocompatibility, and cellular adhesion. The current review focuses on the utilization of different antimicrobial hydrogels based on their sources (natural and synthetic). Further, the review also highlights the strategies for the generation of hydrogels with their advantages and disadvantages and their applications in different biomedical fields. Finally, the prospects in the development of hydrogels-based antimicrobial biomaterials are discussed along with some key challenges encountered during their development and clinical translation.

Physicochemical, electrochemical, and biological characterization of field assisted gold nanocluster-coated barium titanate nanoparticles for biomedical applications.

Fluorescence-based bioimaging is an imperative approach with high clinical relevance in healthcare applications and biomedical research. The field of bioimaging plays an indispensable role in gaining insight into the internal architecture of cells/tissues and comprehending the physiological functions associated with biological systems. With the utility of piezoelectric nanomaterials, the bioelectric interface has been significantly investigated, leading to remarkable clinical relevance. Herein, we have developed barium titanate nanoparticle (BT) coated gold nanoclusters (AuNCs) in the presence and absence of an electromagnetic field (EMF). In this work, the effect of low (0.6 G) and high (2.0 G) EMFs on the structural arrangement of these piezoelectric nanocomposites (ABT) has been extensively studied with the help of X-ray diffraction (XRD), high diffraction resolution transmission electron microscopy (HR-TEM) and X-ray photoelectron spectroscopy (XPS). Furthermore, the two derivatives of ABT i.e. 0.6 ABT and 2.0 ABT have been evaluated for electrochemical behavior for their applicability as a candidate for exploring the bioelectric interface. Additionally, ABT, 0.6 ABT, and 2.0 ABT have been explored for cytocompatibility and bioimaging applications. The proposed piezoelectric nanocomposite, as a multifunctional platform, has enormous proficiency in the field of bioimaging and the capability to be utilized across the bioelectric interface.

Synthesis and antibacterial activity of 2-benzylidene-3-oxobutanamide derivatives against resistant pathogens.

Antibiotic resistance evolves naturally through random mutation. Resistance to antimicrobials is an urgent public health crisis that requires coordinated global action. The ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are primarily responsible for the rise in resistant pathogens. There is an immediate requirement to identify a novel molecular scaffold with potent anti-microbial properties. We developed an efficient one-step synthesis of 2-benzylidene-3-oxobutanamide and its derivatives, which allowed the introduction of an α,ß-unsaturated ketone moiety in the quest to identify a new molecular scaffold. Seven compounds exhibited very good antibacterial activity in vitro against WHO priority drug-resistant bacteria such as methicillin resistant Staphyloccus aureus (MRSA) and Acinetobacter baumannii-Multi drug resistant (MDR-AB). In cultured human embryonic kidney cells and hemolysis assays, the potent compounds displayed minimal toxicity. These findings suggest that these small molecules with excellent diversity have the potential to combat antibacterial resistance.

Gd/hafnium oxide@gold@chitosan core-shell nanoparticles as a platform for multimodal theranostics in oncology research.

In the current study, we synthesized thiolated chitosan-stabilized gold-coated, gadolinium-doped hafnium oxide nanoparticles (CAuGH NPs) with the capability of acting as a multifunctional system to deliver anticancer drug doxorubicin (DOX), to enhance radiosensitization by ROS generation, and to provide magnetic resonance (MR) imaging contrast for biomedical applications.

Polysaccharides, proteins, and synthetic polymers based multimodal hydrogels for various biomedical applications: A review.

Nature-derived or biologically encouraged hydrogels have attracted considerable interest in numerous biomedical applications owing to their multidimensional utility and effectiveness. The internal architecture of a hydrogel network, the chemistry of the raw materials involved, interaction across the interface of counter ions, and the ability to mimic the extracellular matrix (ECM) govern the clinical efficacy of the designed hydrogels. This review focuses on the mechanistic viewpoint of different biologically driven/inspired biomacromolecules that encourages the architectural development of hydrogel networks. In addition, the advantage of hydrogels by mimicking the ECM and the significance of the raw material selection as an indicator of bioinertness is deeply elaborated in the review. Furthermore, the article reviews and describes the application of polysaccharides, proteins, and synthetic polymer-based multimodal hydrogels inspired by or derived from nature in different biomedical areas. The review discusses the challenges and opportunities in biomaterials along with future prospects in terms of their applications in biodevices or functional components for human health issues. This review provides information on the strategy and inspiration from nature that can be used to develop a link between multimodal hydrogels as the main frame and its utility in biomedical applications as the primary target.

Reconstituted Super Paramagnetic Protein "Magnetotransferrin" for Brain Targeting to Attenuate Parkinsonism.

Transferrin is an iron transporting protein consisting of bilobal protein shells (apotransferrin) with dual domains in each lobe, holding an interdomain iron binding cleft. This cleft is useful in synthesizing an iron oxide core inside the transferrin shell. In vitro reconstitution chemistry provides a nano-dimensional synthesis of the mineral core inside the protein shell. The present study demonstrates the synthesis of magnetotransferrin with reconstitution of apotransferrin to form iron oxide nanoparticles within the transferrin. Transmission electron microscopy investigations along with analysis of electronic diffraction patterns and magnetometry studies indicate entrapment of superparamagnetic iron (III) oxide nanoparticles. In vivo/ex vivo imaging of the brain and immunogold staining of brain sections further validate the brain targeting potential of "magnetotransferrin". The in vivo therapeutic potential of magneto transferrin has been demonstrated by induction of TRPV1 magnetic stimuli protein, having an important regulatory role in Parkinsonism management. In an exploration of neuroprotective mechanisms, deacetylation of H3K27 of synuclein has been revealed through the TRPV1-mediated HDAC3 activation in the treatment of Parkinsonism. Thus, this magnetic protein could be a potent candidate for brain targeting, bio-imaging, and therapy of neurological infirmities.

Degradation mechanism of aflatoxin B1 and aflatoxin G1 by salt tolerant Bacillus albus YUN5 isolated from 'doenjang', a traditional Korean food.

Aflatoxins are the mycotoxins that contaminate food and feed and pose health hazards to humans and animals. Here, Bacillus albusYUN5 was isolated from doenjang (Korean fermented soybean paste) and examined for aflatoxin B1 (AFB1) and aflatoxin G1 (AFG1) degradation capabilities. The highest degradation of AFB1 (76.28 ± 0.15%) and AFG1 (98.98 ± 0.00%) was observed in the cell-free supernatant (CFS) ofB. albusYUN5, whereas negligible degradation was observed in intracellular fraction, viable cells, and cell debris. Furthermore, heat (100 °C) and proteinase K treated CFS possessed AFB1 and AFG1 degradation ability, suggesting that substances other than proteins or enzymes are responsible for the degradation. Optimal degradation of AFB1 and AFG1 by the CFS was achieved at 55 °C and 45 °C, respectively, and at pH 7-10 and salt concentration of 0-20%. Liquid chromatography-mass spectroscopy analysis of the degraded products revealed that either the difuran or lactone ring of AFB1 and lactone ring of AFG1 is the main target site by CFS of B. albus YUN5. A slightly better reduction of AFB1 and AFG1 was observed in doenjang treated with CFS and viable cells of B. albus YUN5 compared to those without CFS and B. albus YUN5 treated doenjang during one year of fermentation, suggesting the applicability of B. albus in real food.

Dextran/eudragit S-100 based redox sensitive nanoparticles for colorectal cancer therapy.

Herein, we present disulfide crosslinked dextran/eudragit S-100 nanoparticles (DEEU NPs) (≈55 nm) for colorectal cancer treatment. These redox environment sensitive DEEU NPs are synthesized by simple oxidation of thiolated polymers in air. This approach allows avoiding the use of any additional chemical crosslinker. These DEEU NPs have high encapsulation efficiency for the doxorubicin (DOX) model drug (≈95%). The prepared DEEU NPs are redox sensitive owing to disulfide units and exhibit ≈80% DOX release in the reducing environment of GSH. Additionally, DOX-DEEU NPs display enhanced cytotoxicity for HCT116 cancer cells as compared to free DOX. Annexin V staining results also support the higher anticancer efficiency of DOX-DEEU NPs via induction of apoptosis. In vivo biodistribution results demonstrate that DEEU NPs can remain in the colon region for up to 24 hours. These results indicate that DEEU NPs can act as a promising platform for colorectal cancer treatment.

Curcumin-loaded alginate hydrogels for cancer therapy and wound healing applications: A review.

Hydrogels have emerged as a versatile platform for a numerous biomedical application due to their ability to absorb a huge quantity of biofluids. In order to design hydrogels, natural polymers are an attractive option owing to their biocompatibility and biodegradability. Due to abundance in occurrence, cost effectiveness, and facile crosslinking approaches, alginate has been extensively investigated to fabricate hydrogel matrix. Management of cancer and chronic wounds have always been a challenge for pharmaceutical and healthcare sector. In both cases, curcumin have been shown significant improvement and effectiveness. However, the innate restraints like poor bioavailability, hydrophobicity, and rapid systemic clearance associated with curcumin have restricted its clinical translations. The current review explores the cascade of research around curcumin encapsulated alginate hydrogel matrix for wound healing and cancer therapy. The focus of the review is to emphasize the mechanistic effects of curcumin with its fate inside the cells. Further, the review discusses different approaches to designed curcumin loaded alginate hydrogels along with the parameters that regulates their release behavior. Finally, the review is concluded with emphasize on some key aspect on increasing the efficacy of these hydrogels along with novel strategies to further develop curcumin loaded alginate hydrogel matrix with multifacet applications.

Translational Nanomedicines Across Human Reproductive Organs Modeling on Microfluidic Chips: State-of-the-Art and Future Prospects.

Forecasting the consequence of nanoparticles (NPs) and therapeutically significant molecules before materializing for human clinical trials is a mainstay for drug delivery and screening processes. One of the noteworthy obstacles that has prevented the clinical translation of NP-based drug delivery systems and novel drugs is the lack of effective preclinical platforms. As a revolutionary technology, the organ-on-a-chip (OOC), a coalition of microfluidics and tissue engineering, has surfaced as an alternative to orthodox screening platforms. OOC technology recapitulates the structural and physiological features of human organs along with intercommunications between tissues on a chip. The current review discusses the concept of microfluidics and confers cutting-edge fabrication processes for chip designing. We also outlined the advantages of microfluidics in analyzing NPs in terms of characterization, transport, and degradation in biological systems. The review further elaborates the scope and research on translational nanomedicines in human reproductive organs (testis, placenta, uterus, and menstrual cycle) by taking the advantages offered by microfluidics and shedding light on their potential future implications. Finally, we accentuate the existing challenges for clinical translation and scale-up dynamics for microfluidics chips and emphasize its future perspectives.

A Comprehensive Review on Barium Titanate Nanoparticles as a Persuasive Piezoelectric Material for Biomedical Applications: Prospects and Challenges.

Stimulation of cells with electrical cues is an imperative approach to interact with biological systems and has been exploited in clinical practices over a wide range of pathological ailments. This bioelectric interface has been extensively explored with the help of piezoelectric materials, leading to remarkable advancement in the past two decades. Among other members of this fraternity, colloidal perovskite barium titanate (BaTiO3 ) has gained substantial interest due to its noteworthy properties which includes high dielectric constant and excellent ferroelectric properties along with acceptable biocompatibility. Significant progression is witnessed for BaTiO3 nanoparticles (BaTiO3 NPs) as potent candidates for biomedical applications and in wearable bioelectronics, making them a promising personal healthcare platform. The current review highlights the nanostructured piezoelectric bio interface of BaTiO3 NPs in applications comprising drug delivery, tissue engineering, bioimaging, bioelectronics, and wearable devices. Particular attention has been dedicated toward the fabrication routes of BaTiO3 NPs along with different approaches for its surface modifications. This review offers a comprehensive discussion on the utility of BaTiO3 NPs as active devices rather than passive structural unit behaving as carriers for biomolecules. The employment of BaTiO3 NPs presents new scenarios and opportunity in the vast field of nanomedicines for biomedical applications.

Technological and structural aspects of scaffold manufacturing for cultured meat: recent advances, challenges, and opportunities.

In vitro cultured meat is an emerging area of research focus with an innovative approach through tissue engineering (i.e., cellular engineering) to meet the global food demand. The manufacturing of lab-cultivated meat is an innovative business that alleviates life-threatening environmental issues concerning public health and animal well-being on the global platform. There has been a noteworthy advancement in cultivating artificial meat, but still, there are numerous challenges that impede the swift headway of lab-grown meat production at a commercially large scale. In this review, we focus on the manufacturing of edible scaffolds for cultured meat production. In brief, first an introduction to cultivating artificial meat and its current scenario in the market is provided. Further, a discussion on the understanding of composition, cellular, and molecular communications in muscle tissue is presented, which are vital to scaling up the production of lab-grown meat. In continuation, the major components (e.g., cells, biomaterial scaffolds, and their manufacturing technologies, media, and potential bioreactors) for cultured meat production are conferred followed by a comprehensive discussion on the most recent advances in lab-cultured meat. Finally, existing challenges and opportunities including future research perspectives for scaling-up cultured meat production are discussed with conclusive interpretations.

Triple-Networked Hybrid Hydrogels Reinforced with Montmorillonite Clay and Graphene Nanoplatelets for Soft and Hard Tissue Regeneration.

Hydrogel is a three-dimensional (3D) soft and highly hydrophilic, polymeric network that can swell in water and imbibe a high amount of water or biological fluids. Hydrogels have been used widely in various biomedical applications. Hydrogel may provide a fluidic tissue-like 3D microenvironment by maintaining the original network for tissue engineering. However, their low mechanical performances limit their broad applicability in various functional tissues. This property causes substantial challenges in designing and preparing strong hydrogel networks. Therefore, we report the triple-networked hybrid hydrogel network with enhanced mechanical properties by incorporating dual-crosslinking and nanofillers (e.g., montmorillonite (MMT), graphene nanoplatelets (GNPs)). In this study, we prepared hybrid hydrogels composed of polyacrylamide, poly (vinyl alcohol), sodium alginate, MMT, and MMT/GNPs through dynamic crosslinking. The freeze-dried hybrid hydrogels showed good 3D porous architecture. The results exhibited a magnificent porous structure, interconnected pore-network surface morphology, enhanced mechanical properties, and cellular activity of hybrid hydrogels.

Redox responsive poly(allylamine)/eudragit S-100 nanoparticles for dual drug delivery in colorectal cancer.

Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the need of any external crosslinking agent for dual drug delivery. PAEU NPs can effectively encapsulate both hydrophilic doxorubicin (DOX) and hydrophobic curcumin (Cur) drug with ≈85 % and ≈97 % encapsulation efficiency respectively. Here, the combination of drugs having different anticancer mechanism offers the possibility of developing nanosystem with enhanced anticancer efficacy. The developed PAEU NPs show good colloidal stability and low drug release under physiological conditions, while high DOX (≈98 %) and Cur (≈93 %) release is observed in reducing environment (10 mM GSH). Further, DOX and Cur loaded PAEU NPs exhibit higher cancer cell killing efficiency as compared to individual free drugs. In vivo biodistribution studies with Balb/C mice display the retention of PAEU NPs in the colon region up to 24 h presenting the developed approach as an efficient way for colorectal cancer therapy.

Enzyme-Triggered Crosslinked Hybrid Hydrogels for Bone Tissue Engineering.

The quest to develop state-of-the-art hydrogels for bone tissue engineering has accompanied substantial innovation and significant progression in the field of bioactive hydrogels. Still, there is scope for advancement in this cell-friendly and biocompatible scaffold system. The crosslinking approaches used for hydrogel synthesis plays a decisive role in guiding and regulating the mechanical stability, network framework, macroscopic architect, immunological behaviors, and cellular responses. Until recently, enzyme-based crosslinking strategies were considered as the pinnacle in designing efficient hybrid hydrogel systems. A variety of enzymes have been explored for manufacturing hydrogels while taking the advantage of the biocompatible nature, specificity, ability to produce nontoxic by products and high efficiency of enzymes. The current review focuses on the utility of different enzymes as crosslinking agents for hydrogel formation with their application in bone tissue engineering. The field of enzyme crosslinked hydrogel synthesis is rapidly maturing with a lot of opportunities to be explored in bone tissue engineering. Enzyme-based in situ and externally crosslinked hydrogels for bone regeneration is an attractive field, and with innovation in using engineered enzymes this field will continue to flourish with clinical orientation.

Manufacturing functional hydrogels for inducing angiogenic-osteogenic coupled progressions in hard tissue repairs: prospects and challenges.

In large bone defects, inadequate vascularization within the engineered constructs has been a major challenge in developing clinically impactful products. It is fairly determined that bone tissues and blood vessels are established concurrently throughout tissue repairs after an injury. Thus, the coupling of angiogenesis-osteogenesis is an essential course of action in bone tissue restoration. The manufacture of biomaterial-based scaffolds plays a decisive role in stimulating angiogenic and osteogenic progressions (instruction of neovascularization and bone mineralization). Bone hydrogels with optimal conditions are more efficient at healing bone defects. There has been a remarkable advancement in producing bone substitutes in the tissue engineering area, but the sufficient and timely vascularization of engineered constructs for optimal tissue integration and regeneration is lacking due to mismatch in the scaffold characteristics and new bone tissue reconstruction. Therefore, various key challenges remain to be overcome. A deep understanding of angiogenesis and osteogenesis progressions is required to manufacture bone hydrogels with satisfactory results. The current review briefly discusses the fundamentals of bone tissues, the significance of angiogenesis-osteogenesis progressions and their inducers, the efficacy of biomaterials and composite hydrogel-promoted neo-vasculogenesis (i.e. angiogenesis) and bone mineralization (i.e. osteogenesis), and related challenges, including future research directions.

Biodegradable disulfide crosslinked chitosan/stearic acid nanoparticles for dual drug delivery for colorectal cancer.

Herein, redox responsive chitosan/stearic acid nanoparticles (CSSA NPs) (≈200 nm) are developed for dual drug delivery. These degradable nanoparticles are prepared based on disulfide (SS) crosslinking chemistry avoiding the use of any external crosslinking agent. CSSA NPs are further loaded with both DOX (hydrophilic) and curcumin (hydrophobic) drugs with ≈86 % and ≈82 % encapsulation efficiency respectively. This approach of combining anticancer therapeutics having different mode of anticancer action allows to develop systems for cancer therapy with enhanced efficacy. In vitro drug release experiments clearly exhibit the low leakage of drug under physiological conditions while ≈98 % DOX and ≈96 % curcumin is released after 136 h under GSH reducing conditions. The cytotoxicity experiments against HCT116 cells demonstrate higher cytotoxicity of dual drug loaded CSSA NPs. In vivo biodistribution experiments with c57bl/6j mice confirms the retention of CSSA NPs in the colon area up to 24 h exhibiting their potential for colorectal cancer therapy.

Advances in Hydrogel-Based Microfluidic Blood-Brain-Barrier Models in Oncology Research.

The intrinsic architecture and complexity of the brain restricts the capacity of therapeutic molecules to reach their potential targets, thereby limiting therapeutic possibilities concerning neurological ailments and brain malignancy. As conventional models fail to recapitulate the complexity of the brain, progress in the field of microfluidics has facilitated the development of advanced in vitro platforms that could imitate the in vivo microenvironments and pathological features of the blood-brain barrier (BBB). It is highly desirous that developed in vitro BBB-on-chip models serve as a platform to investigate cancer metastasis of the brain along with the possibility of efficiently screening chemotherapeutic agents against brain malignancies. In order to improve the proficiency of BBB-on-chip models, hydrogels have been widely explored due to their unique physical and chemical properties, which mimic the three-dimensional (3D) micro architecture of tissues. Hydrogel-based BBB-on-chip models serves as a stage which is conducive for cell growth and allows the exchange of gases and nutrients and the removal of metabolic wastes between cells and the cell/extra cellular matrix (ECM) interface. Here, we present recent advancements in BBB-on-chip models targeting brain malignancies and examine the utility of hydrogel-based BBB models that could further strengthen the future application of microfluidic devices in oncology research.